EFFECTIVENESS OF PUBLIC HEALTH MEASURES IN REDUCING THE INCIDENCE OF COVID-19, SARS-COV-2 TRANSMISSION, AND COVID-19 MORTALITY: SYSTEMATIC REVIEW ...

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                                      Effectiveness of public health measures in reducing the incidence
                                      of covid-19, SARS-CoV-2 transmission, and covid-19 mortality:
                                      systematic review and meta-analysis
                                      Stella Talic,1,2 Shivangi Shah,1 Holly Wild,1,3 Danijela Gasevic,1,4 Ashika Maharaj,1
                                      Zanfina Ademi,1,2 Xue Li,4,6 Wei Xu,4 Ines Mesa-Eguiagaray,4 Jasmin Rostron,4
                                      Evropi Theodoratou,4,5 Xiaomeng Zhang,4 Ashmika Motee,4 Danny Liew,1,2 Dragan Ilic1

1
 School of Public Health and          ABSTRACT                                               37 assessed multiple public health measures as a
Preventive Medicine, Monash           OBJECTIVE                                              “package of interventions.” Eight of 35 studies were
University, Melbourne, 3004 VIC,      To review the evidence on the effectiveness of         included in the meta-analysis, which indicated a
Australia
2                                     public health measures in reducing the incidence of    reduction in incidence of covid-19 associated with
 Monash Outcomes Research
and health Economics (MORE)           covid-19, SARS-CoV-2 transmission, and covid-19        handwashing (relative risk 0.47, 95% confidence
Unit, Monash University, VIC,         mortality.                                             interval 0.19 to 1.12, I2=12%), mask wearing (0.47,
Australia                                                                                    0.29 to 0.75, I2=84%), and physical distancing (0.75,
3
                                      DESIGN
 Torrens University, VIC, Australia                                                          0.59 to 0.95, I2=87%). Owing to heterogeneity of
4
                                      Systematic review and meta-analysis.
 Centre for Global Health, The                                                               the studies, meta-analysis was not possible for the
Usher Institute, University of        DATA SOURCES
Edinburgh, Edinburgh, UK                                                                     outcomes of quarantine and isolation, universal
                                      Medline, Embase, CINAHL, Biosis, Joanna Briggs,
5
 Cancer Research UK Edinburgh                                                                lockdowns, and closures of borders, schools, and
                                      Global Health, and World Health Organization
Centre, MRC Institute of Genetics                                                            workplaces. The effects of these interventions were
                                      COVID-19 database (preprints).
and Molecular Medicine,                                                                      synthesised descriptively.
University of Edinburgh,              ELIGIBILITY CRITERIA FOR STUDY SELECTION
Edinburgh, UK                                                                                CONCLUSIONS
                                      Observational and interventional studies that
6
 School of Public Health and                                                                 This systematic review and meta-analysis suggests
                                      assessed the effectiveness of public health measures
The Second Affiliated Hospital,                                                              that several personal protective and social measures,
Zhejiang University School of         in reducing the incidence of covid-19, SARS-CoV-2
                                                                                             including handwashing, mask wearing, and physical
Medicine, Hangzhou, China             transmission, and covid-19 mortality.
                                                                                             distancing are associated with reductions in the
Correspondence to: S Talic            MAIN OUTCOME MEASURES
stella.talic@monash.edu                                                                      incidence covid-19. Public health efforts to implement
(ORCID 0000-0001-7739-3381)           The main outcome measure was incidence of              public health measures should consider community
Additional material is published      covid-19. Secondary outcomes included SARS-CoV-2       health and sociocultural needs, and future research
online only. To view please visit     transmission and covid-19 mortality.                   is needed to better understand the effectiveness of
the journal online.
                                      DATA SYNTHESIS                                         public health measures in the context of covid-19
Cite this as: BMJ 2021;375:e068302
http://dx.doi.org/10.1136/            DerSimonian Laird random effects meta-analysis was     vaccination.
bmj-2021-068302                       performed to investigate the effect of mask wearing,   SYSTEMATIC REVIEW REGISTRATION
Accepted: 21 October 2021             handwashing, and physical distancing measures          PROSPERO CRD42020178692.
                                      on incidence of covid-19. Pooled effect estimates
                                      with corresponding 95% confidence intervals were
                                      computed, and heterogeneity among studies was          Introduction
                                      assessed using Cochran’s Q test and the I2 metrics,    The impact of SARS-CoV-2 on global public health and
                                      with two tailed P values.                              economies has been profound.1 As of 14 October 2021,
                                                                                             there were 239 007 759 million cases of confirmed
                                      RESULTS
                                                                                             covid-19 and 4 871 841 million deaths with covid-19
                                      72 studies met the inclusion criteria, of which 35
                                                                                             worldwide.2
                                      evaluated individual public health measures and
                                                                                                A variety of containment and mitigation strategies
 WHAT IS ALREADY KNOWN ON THIS TOPIC                                                         have been adopted to adequately respond to covid-19,
                                                                                             with the intention of deferring major surges of patients
 Public health measures have been identified as a preventive strategy for
                                                                                             in hospitals and protecting the most vulnerable
 influenza pandemics
                                                                                             people from infection, including elderly people and
 The effectiveness of such interventions in reducing the transmission of SARS-               those with comorbidities.3 Strategies to achieve these
 CoV-2 is unknown                                                                            goals are diverse, commonly based on national risk
 WHAT THIS STUDY ADDS                                                                        assessments that include estimation of numbers of
                                                                                             patients requiring hospital admission and availability
 The findings of this review suggest that personal and social measures, including
                                                                                             of hospital beds and ventilation support.
 handwashing, mask wearing, and physical distancing are effective at reducing
                                                                                                Globally, vaccination programmes have proved
 the incidence of covid-19
                                                                                             to be safe and effective and save lives.4 5 Yet most
 More stringent measures, such as lockdowns and closures of borders, schools,                vaccines do not confer 100% protection, and it is not
 and workplaces need to be carefully assessed by weighing the potential negative             known how vaccines will prevent future transmission
 effects of these measures on general populations                                            of SARS-CoV-2,6 given emerging variants.7-9 The
 Further research is needed to assess the effectiveness of public health measures            proportion of the population that must be vaccinated
 after adequate vaccination coverage                                                         against covid-19 to reach herd immunity depends

the bmj | BMJ 2021;375:e068302 | doi: 10.1136/bmj-2021-068302                                                                                       1
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                                                                                                                                                                              BMJ: first published as 10.1136/bmj-2021-068302 on 17 November 2021. Downloaded from http://www.bmj.com/ on 27 December 2021 by guest. Protected by copyright.
                                      greatly on current and future variants.10 This                          public health measures, particularly in policy decision
                                      vaccination threshold varies according to the country                   making.19
                                      and population’s response, types of vaccines, groups                       Previous systematic reviews on the effectiveness of
                                      prioritised for vaccination, and viral mutations,                       public health measures to treat covid-19 lacked the
                                      among other factors.6 Until herd immunity to covid-19                   inclusion of analytical studies,20 a comprehensive
                                      is reached, regardless of the already proven high                       approach to data synthesis (focusing only on one
                                      vaccination rates,11 public health preventive strategies                measure),21 a rigorous assessment of effectiveness
                                      are likely to remain as first choice measures in disease                of public health measures,22 an assessment of the
                                      prevention,12 particularly in places with a low uptake                  certainty of the evidence,23 and robust methods for
                                      of covid-19 vaccination. Measures such as lockdown                      comparative analysis.24 To tackle these gaps, we
                                      (local and national variant), physical distancing,                      performed a systematic review of the evidence on the
                                      mandatory use of face masks, and hand hygiene have                      effectiveness of both individual and multiple public
                                      been implemented as primary preventive strategies to                    health measures in reducing the incidence of covid-19,
                                      curb the covid-19 pandemic.13                                           SARS-CoV-2 transmission, and covid-19 mortality.
                                         Public health (or non-pharmaceutical) interventions                  When feasible we also did a critical appraisal of the
                                      have been shown to be beneficial in fighting respiratory                evidence and meta-analysis.
                                      infections transmitted through contact, droplets,
                                      and aerosols.14 15 Given that SARS-CoV-2 is highly                      Methods
                                      transmissible, it is a challenge to determine which                     This   systematic  review   and      meta-analysis
                                      measures might be more effective and sustainable for                    were conducted in accordance with PRISMA25
                                      further prevention.                                                     (supplementary material 1, table 1) and with
                                         Substantial benefits in reducing mortality were                      PROSPERO (supplementary material 1, table 2).
                                      observed in countries with universal lockdowns in
                                      place, such as Australia, New Zealand, Singapore,                       Eligibility criteria
                                      and China. Universal lockdowns are not, however,                        Articles that met the population, intervention,
                                      sustainable, and more tailored interventions need                       comparison, outcome, and study design criteria
                                      to be considered; the ones that maintain social lives                   were eligible for inclusion in this systematic review
                                      and keep economies functional while protecting                          (supplementary material 1, table 3). Specifically,
                                      high risk individuals.16 17 Substantial variation exists                preventive public health measures that were tested
                                      in how different countries and governments have                         independently were included in the main analysis.
                                      applied public health measures,18 and it has proved a                   Multiple measures, which generally contain a “package
                                      challenge for assessing the effectiveness of individual                 of interventions”, were included as supplementary
                                                                                                              material owing to the inability to report on the
                                                                                                              individual effectiveness of measures and comparisons
               Visual Abstract                 Hands, face, space v covid-19                                  on which package led to enhanced outcomes. The
                                               Effectiveness of public health measures
                                                                                                              public health measures were identified from published
         Summary                 Several public health measures, including handwashing, mask                  World Health Organization sources that reported
                                 wearing, and physical distancing, were associated with a reduction           on the effectiveness of such measures on a range of
                                 in incidence of covid-
                                                                                                              communicable diseases, mostly respiratory infections,
         Study design                                                                                         such as influenza.
                                    72 Met inclusion criteria           37 Excluded from analysis                Given that the scientific community is concerned
         Systematic review
         and meta-analysis
                                                                    Assessed multiple measures                about the ability of the numerous mathematical
                                                                    as a “package of interventions”
                                      Evaluated individual                                                    models, which are based on assumptions, to predict
                                 35
      Risk of bias                    measures                                                                the course of virus transmission or effectiveness of
         0 Low                                                          27 Excluded from analysis             interventions,26 this review focused only on empirical
         6 Medium                                                   Owing to heterogeneity of studies         studies. We excluded case reports and case studies,
         2 Serious               8 Included in meta-analysis        (effects synthesised descriptively)
                                                                                                              modelling and simulation studies, studies that
                                                                                                              provided a graphical summary of measures without
         3                                6                                  5                                clear statistical assessments or outputs, ecological
                                                                                                              studies that provided a descriptive summary of the
                                                                                                              measures without assessing linearity or having
     Assessed handwashing              Assessed mask wearing             Assessed physical distancing
                                                                                                              comparators, non-empirical studies (eg, commentaries,
                                                                                                              editorials, government reports), other reviews, articles
                                                                                                              involving only individuals exposed to other pathogens
         Outcomes                                               Relative risk % CI
                                                                                                              that can cause respiratory infections, such as severe
     Random effects model results        .                      .                                   
                                                                                                              acute respiratory syndrome or Middle East respiratory
     Handwashing
                                                                                                              syndrome, and articles in a language other than English.
     Mask wearing
     Physical distancing                                                                                      Information sources
      http://bit.ly/BMJc19phm                                              © 2021 BMJ Publishing group Ltd.   We carried out electronic searches of Medline,
                                                                                                              Embase, CINAHL (Cumulative Index to Nursing and

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                                                                                                                                                           BMJ: first published as 10.1136/bmj-2021-068302 on 17 November 2021. Downloaded from http://www.bmj.com/ on 27 December 2021 by guest. Protected by copyright.
                                Allied Health Literature, Ebsco), Global Health, Biosis,       with corresponding 95% confidence intervals were
                                Joanna Briggs, and the WHO COVID-19 database (for              reported for the associations between the public
                                preprints). A clinical epidemiologist (ST) developed           health measures and incidence of covid-19. When
                                the initial search strategy, which was validated by two        necessary, we transformed effect metrics derived from
                                senior medical librarians (LR and MD) (supplementary           different studies to allow pooled analysis. We used the
                                material 1, table 4). The updated search strategy was          Dersimonian Laird random effects model to estimate
                                last performed on 7 June 2021. All citations identified        pooled effect estimates along with corresponding 95%
                                from the database searches were uploaded to                    confidence intervals for each measure. Heterogeneity
                                Covidence, an online software designed for managing            among individual studies was assessed using
                                systematic reviews,27 for study selection.                     the Cochran Q test and the I2 test.31 All statistical
                                                                                               analyses were conducted in R (version 4.0.3) and all
                                Study selection                                                P values were two tailed, with P=0.05 considered to
                                Authors ST, DG, SS, AM, ET, JR, XL, WX, IME, and XZ            be significant. For the remaining studies, when meta-
                                independently screened the titles and abstracts and            analysis was not feasible, we reported the results in a
                                excluded studies that did not match the inclusion              narrative synthesis.
                                criteria. Discrepancies were resolved in discussion
                                with the main author (ST). The same authors retrieved          Public and patient involvement
                                full text articles and determined whether to include           No patients or members of the public were directly
                                or exclude studies on the basis of predetermined               involved in this study as no primary data were
                                selection criteria. Using a pilot tested data extraction       collected. A member of the public was, however, asked
                                form, authors ST, SS, AM, JR, XL, WX, AM, IME, and             to read the manuscript after submission.
                                XZ independently extracted data on study design,
                                intervention, effect measures, outcomes, results, and          Results
                                limitations. ST, SS, AM, and HW verified the extracted         A total of 36 729 studies were initially screened,
                                data. Table 5 in supplementary material 1 provides             of which 36 079 were considered irrelevent. After
                                the specific criteria used to assess study designs.            exclusions, 650 studies were eligible for full text
                                Given the heterogeneity and diversity in how studies           review and 72 met the inclusion criteria. Of these
                                defined public health measures, we took a common               studies, 35 assessed individual interventions and were
                                approach to summarise evidence of these interventions          included in the final synthesis of results (fig 1) and 37
                                (supplementary material 1, table 6).                           assessed multiple interventions as a package and are
                                                                                               included in supplementary material 3, tables 2 and
                                Risk of bias within individual studies                         3. The included studies comprised 34 observational
                                SS, JR, XL, WX, IME, and XZ independently assessed             studies and one interventional study, eight of which
                                risk of bias for each study, which was cross checked           were included in the meta-analysis.
                                by ST and HW. For non-interventional observational
                                studies, a ROBINS-I (risk of bias in non-randomised            Risk of bias
                                studies of interventions) risk of bias tool was used.28        According to the ROBINS-I tool,28 the risk of bias was
                                For interventional studies, a revised tool for assessing       rated as low in three studies,32-34 moderate in 24
                                risk of bias in randomised trials (RoB 2) tool was             studies,35-58 and high to serious in seven studies.59-65
                                used.29 Reviewers rated each domain for overall risk of        One important source of serious or critical risk of bias
                                bias as low, moderate, high, or serious/critical.              in most of the included studies was major confounding,
                                                                                               which was difficult to control for because of the novel
                                Data synthesis                                                 nature of the pandemic (ie, natural settings in which
                                The DerSimonian and Laird method was used for                  multiple interventions might have been enforced at
                                random effects meta-analysis, in which the standard            once, different levels of enforcement across regions,
                                error of the study specific estimates was adjusted to          and uncaptured individual level interventions
                                incorporate a measure of the extent of variation, or           such as increased personal hygiene). Variations in
                                heterogeneity, among the effects observed for public           testing capacity and coverage, changes to diagnostic
                                health measures across different studies. It was               criteria, and access to accurate and reliable outcome
                                assumed that the differences between studies are a             data on covid-19 incidence and covid-19 mortality,
                                result of different, yet related, intervention effects being   was a source of measurement bias for numerous
                                estimated. If fewer than five studies were included in         studies (fig 2). These limitations were particularly
                                meta-analysis, we applied a recommended modified               prominent early in the pandemic, and in low income
                                Hartung-Knapp-Sidik-Jonkman method.30                          environments.47 52 62 63 65 The randomised controlled
                                                                                               trial66 was rated as moderate risk of bias according
                                Statistical analysis                                           to the ROB-2 tool. Missing data, losses to follow-up,
                                Because of the differences in the effect metrics               lack of blinding, and low adherence to intervention
                                reported by the included studies, we could only                all contributed to the reported moderate risk. Tables 1
                                perform quantitative data synthesis for three                  and 2 in supplementary material 2 summarise the risk
                                interventions: handwashing, face mask wearing,                 of bias assessment for each study assessing individual
                                and physical distancing. Odds ratios or relative risks         measures.

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                                                         51 878
                                                                                                        States (n=9), Europe (n=7), the Middle East (n=3), Africa
                                                  Records identified                                     (n=3), South America (n=1), and Australia (n=1). Thirty
             18 532 Embase                    6901 CINAHL                       3173 Preprints WHO      four of the studies were observational and one was a
             15 399 Medline                   7873 Joanna Briggs, Biosis,            COVID-19           randomised controlled trial. The study designs of the
                                                   and Global Health                 database           observational studies comprised natural experiments
                                                                                                        (n=11), quasi-experiments (n=3), a prospective cohort
                                                                              15 149                    (n=1), retrospective cohorts (n=8), case-control (n=2),
                                                                            Duplicates                  and cross sectional (n=9). Twenty six studies assessed
                                                                                                        social measures,32 34 35 37-42 44 46-48 52 53 55-61 63-65 67
                                                          36 729                                        12      studies      assessed           personal      protective
                                                     Records screened                                   measures,36 43 45 49 50 57 58 60 63 66 68 three studies assessed
                                                                                                        travel related measures,54 58 62 and one study assessed
                                                                              36 079                    environmental measures57 (some interventions
                                                                         Records excluded               overlapped across studies). The most commonly
                                                                                                        measured outcome was incidence of covid-19 (n=18),
                                                               650                                      followed by SARS-CoV-2 transmission, measured as
                                                 Full text articles assessed                            reproductive number, growth number, or epidemic
                                                                                                        doubling time (n=13), and covid-19 mortality (n=8).
                                                                                   578                  Table 1 in supplementary material 3 provides detailed
                                                                    Full text articles excluded
                                                                                                        information on each study.
                                                             148   Inadequate study design
                                                             120   Editorials or commentaries
                                                             136   Simulation studies                   Effects of interventions
                                                              89   No reported or ineligible outcomes   Personal protective measures
                                                              33   Ineligible setting or population     Handwashing and covid-19 incidence—Three studies
                                                              15   Ineligible intervention
                                                              15   Reports                              with a total of 292 people infected with SARS-CoV-2 and
                                                              22   Duplicates                           10 345 participants were included in the analysis of the
                                                                                                        effect of handwashing on incidence of covid-19.36 60 63
                                                    72                                                  Overall pooled analysis suggested an estimated 53%
                                                 Total                                                  non-statistically significant reduction in covid-19
             35 Studies assessing individual interventions                                              incidence (relative risk 0.47, 95% confidence interval
                8 Included in quantitative synthesis                                                    0.19 to 1.12, I2=12%) (fig 3). A sensitivity analysis
               27 Included in qualitative synthesis
             37 Studies assessing multiple interventions (see supplementary material)                   without adjustment showed a significant reduction in
                                                                                                        covid-19 incidence (0.49, 0.33 to 0.72, I2=12%) (fig
Fig 1 | Flow of articles through the review. WHO=World Health Organization                              4). Risk of bias across the three studies ranged from
                                                                                                        moderate36 60 to serious or critical63 (fig 2).
                                              Study characteristics                                        Mask wearing and covid-19 incidence—Six studies
                                              Studies assessing individual measures                     with a total of 2627 people with covid-19 and 389 228
                                              Thirty five studies provided estimates on the             participants were included in the analysis examining the
                                              effectiveness of an individual public health measures.    effect of mask wearing on incidence of covid-19 (table
                                              The studies were conducted in Asia (n=11), the United     1).36 43 57 60 63 66 Overall pooled analysis showed a 53%
                                                                                                        reduction in covid-19 incidence (0.47, 0.29 to 0.75),
                             Risk of bias                                                               although heterogeneity between studies was substantial
                               Serious or critical    High     Moderate        Low                      (I2=84%) (fig 5). Risk of bias across the six studies ranged
                        40                                                                              from moderate36 57 60 66 to serious or critical43 63 (fig 2).
        No of studies

                                                                                                           Mask wearing and transmission of SARS-CoV-2,
                        30                                                                              covid-19 incidence, and covid-19 mortality—The results
                                                                                                        of additional studies that assessed mask wearing (not
                                                                                                        included in the meta-analysis because of substantial
                        20
                                                                                                        differences in the assessed outcomes) indicate
                                                                                                        a reduction in covid-19 incidence, SARS-CoV-2
                        10                                                                              transmission, and covid-19 mortality. Specifically,
                                                                                                        a natural experiment across 200 countries showed
                         0                                                                              45.7% fewer covid-19 related mortality in countries
                                                                                                        where mask wearing was mandatory (table 1).49
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                                                                                                        Another natural experiment study in the US reported a
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                                                                                                        29% reduction in SARS-CoV-2 transmission (measured
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                                                                                                        as the time varying reproductive number Rt) (risk ratio
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                                                                                                        0.71, 95% confidence interval 0.58 to 0.75) in states
                                cip
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                                                                                                        where mask wearing was mandatory.58
                         pa
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Fig 2 | Summary of risk of bias across studies assessing individual measures using risk                    A comparative study in the Hong Kong Special
of bias in non-randomised studies of interventions (ROBINS-I) tool                                      Administrative Region reported a statistically

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                                             Study                             Intervention              Relative risk       Weight        Relative risk
                                                                                                           (95% CI)           (%)            (95% CI)

                                              Doung-Ngern 2020                  Handwashing                                      19.1   0.34 (0.13 to 0.88)
                                              Lio 2021                           Handwashing                                      17.8   0.30 (0.11 to 0.81)
                                              Xu 2020                            Handwashing                                      63.1   0.58 (0.40 to 0.84)
                                             Random effects model (adjusted) Handwashing                                         100.0   0.47 (0.19 to 1.12)
                                             Test for heterogeneity: τ2=0.053; P=0.32; I2=12%
                                                                                                0.1        0.5 1     2       5

                                Fig 3 | Meta-analysis of evidence on association between handwashing and incidence of covid-19 using modified
                                Hartung-Knapp-Sidik-Jonkman adjusted random effect model

                                significant lower cumulative incidence of covid-19                    on the incidence of covid-19.37 53 57 60 63 Overall pooled
                                associated with mask wearing than in selected countries               analysis indicated a 25% reduction in incidence of
                                where mask wearing was not mandatory (table 1).68                     covid-19 (relative risk 0.75, 95% confidence interval
                                Similarly, another natural experiment involving 15                    0.59 to 0.95, I2=87%) (fig 6). Heterogeneity among
                                US states reported a 2% statistically significant daily               studies was substantial, and risk of bias ranged from
                                decrease in covid-19 transmission (measured as case                   moderate37 53 57 60 to serious or critical63 (fig 2).
                                growth rate) at ≥21 days after mask wearing became
                                mandatory,50 whereas a cross sectional study reported                 Physical distancing and transmission of SARS-CoV-2
                                that a 10% increase in self-reported mask wearing                     and covid-19 mortality
                                was associated with greater odds for control of SARS-                 Studies that assessed physical distancing but were not
                                CoV-2 transmission (adjusted odds ratio 3.53, 95%                     included in the meta-analysis because of substantial
                                confidence interval 2.03 to 6.43).45 The five studies                 differences in outcomes assessed, generally reported
                                were rated at moderate risk of bias (fig 2).                          a positive effect of physical distancing (table 2). A
                                                                                                      natural experiment from the US reported a 12%
                                Environmental measures                                                decrease in SARS-CoV-2 transmission (relative risk
                                Disinfection in household and covid-19 incidence                      0.88, 95% confidence interval 0.86 to 0.89),40 and
                                Only one study, from China, reported the association                  a quasi-experimental study from Iran reported a
                                between disinfection of surfaces and risk of secondary                reduction in covid-19 related mortality (β −0.07,
                                transmission of SARS-CoV-2 within households (table                   95% confidence interval −0.05 to −0.10; P
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 Table 1 | Study characteristics and main results from studies that assessed individual personal protective and environmental measures
                                                Public health                                Outcome           Study                                              Risk of
 Reference, country         Study design        measure               Sample size            measure           duration Effect estimates: conclusions             bias
 Doung-Ngern et al,63       Case-control        Handwashing           211 cases, 839        Incidence          1-31 MarRegular handwashing: adjusted odds         Serious or
 Thailand                                                             controls                                 2020    ratio 0.34 (95% confidence interval 0.13   critical
                                                                                                                       to 0.87): associated with lower risk of
                                                                                                                       SARS-CoV-2*
 Lio et al,36 China         Case-control        Handwashing         24 cases, 1113      Incidence         17 Mar-15    Adjusted odds ratio 0.30 (95%              Moderate
                                                                    controls                              Apr 2020     confidence interval 0.11 to 0.80):
                                                                                                                       reduction in odds of becoming
                                                                                                                       infectious*
 Xu et al,60 China          Cross sectional     Handwashing         n=8158              Incidence         22 Feb-5 Mar Relative risk 3.53 (95% confidence         Moderate
                            comparative                                                                   2020         interval 1.53 to 8.15): significantly
                                                                                                                       increased risk of infection with no
                                                                                                                       handwashing*
 Bundgaard et al,66         Randomised          Mask wearing        2392 cases, 2470 Incidence            Apr and May Odds ratio 0.82 (95% confidence             Moderate
 Denmark                    controlled                              controls                              2020         interval 0.54 to 1.23): 46% reduction to
                                                                                                                       23% increase in infection*
 Doung-Ngern et al,63       Case-control        Mask wearing        211 cases, 839      Incidence         1-31 Mar     Adjusted odds ratio 0.23 (95%              Serious or
 Thailand                                                           controls                              2020         confidence interval 0.09 to 1.60):         critical
                                                                                                                       associated with lower risk of SARS-CoV-2
                                                                                                                       infection*
 Lio et al,36 China         Case-control        Mask wearing        24 cases, 1113      Incidence         17 Mar-15    Odds ratio 0.30 (95% confidence            Moderate
                                                                    controls                              Apr 2020     interval 0.10 to 0.86): 70% risk
                                                                                                                       reduction*
 Xu et al,60 China          Cross sectional     Mask wearing        8158 people         Incidence         22 Feb-5 Mar Relative risk 12.38 (95% confidence        Moderate
                            comparative                                                                   2020         interval 5.81 to 26.36): significantly
                                                                                                                       increased risk of infection*
 Krishnamachari et al,43    Natural             Mask wearing        50 states           Incidence         Apr 2020     3-6 months, adjusted odds ratio 1.61       Serious or
 US                         experiment                                                  (cumulative rate)              (95% confidence interval 1.23 to 2.10):    critical
                                                                                                                       >6 months, 2.16 (1.64 to 2.88): higher
                                                                                                                       incidence rate with later mask mandate
                                                                                                                       than with mask mandate in first month*
 Wang et al,57 China        Retrospective       Mask wearing        335 people          Incidence         28 Feb-27    Odds ratio 0.21 (95% confidence            Moderate
                            cohort                                                      (assessed as      Mar 2020     interval 0.06 to 0.79): 79% reduction in
                                                                                        attack rate†)                  transmission of SARS-CoV-2*
 Cheng et al,68 China       Longitudinal        Mask wearing        961 cases (HKSAR), Incidence          31 Dec 2019- Incidence rate 49.6% (South Korea) v       Moderate
                            comparative         (South Korea v      average control not                   8 Apr 2020   11.8% (HKSAR) P
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                                             Study                              Intervention               Relative risk     Weight       Relative risk
                                                                                                             (95% CI)         (%)           (95% CI)

                                              Bundagaard 2021                   Mask wearing                                     22.2   0.82 (0.54 to 1.24)
                                              Doung-Ngern 2020                  Mask wearing                                      7.6   0.23 (0.05 to 0.97)
                                              Krishnamachari 2021               Mask wearing                                     26.6   0.77 (0.71 to 0.84)
                                              Lio 2021                          Mask wearing                                     11.1   0.30 (0.10 to 0.88)
                                              Xu 2020                           Mask wearing                                     23.6   0.34 (0.24 to 0.48)
                                              Wang 2020                         Mask wearing                                      8.9   0.21 (0.06 to 0.76)
                                             Random effects model               Mask wearing                                    100.0   0.47 (0.29 to 0.75)
                                             Test for heterogeneity: τ2=0.214; P
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 Table 2 | Study characteristics and main results from studies assessing individual social measures
                                              Public health                                      Study dura-                                                           Risk of
  Reference, country        Study design      measure       Sample size        Outcome           tion              Effect estimates: conclusions                       bias
 Jarvis et al,65 UK         Cross sectional   Stay at home 1356 cases          R0                Feb-24 Mar       R0: pre-intervention 3.6, post-intervention 0.60     Serious or
                                              or isolation                                       2020             (95% confidence interval 0.37 to 0.89): 3.0 R0       critical
                                                                                                                  decrease
 Khosravi et al,55 Iran     Cross sectional   Stay at home   993 cases         R0                20 Feb-01 Apr    R0: pre-intervention 2.70 (95% confidence            Moderate
                                              or isolation                                       2020             interval 2.10 to 3.40), post-intervention 1.13
                                                                                                                  (1.03 to 1.25): 1.5 R0 decrease
 Dreher et al,41 US         Retrospective     Stay at home   49 states and     R0                NS               Odds ratio 0.07 (95% confidence interval 0.01        Low
                            cohort            or isolation   territories                                          to 0.37): decrease in odds of having a positive
                                                                                                                  R0 result*
 Liu et al,58 US            Natural           Stay at home   50 states         Rt                21 Jan-31 May    Risk ratio 0.49 (95% confidence interval 0.43 to     Moderate
                            experiment        or isolation                                       2020             0.54): contributed about 51% to reduction in Rt*
 Alfano et al,52 Italy      Natural           Lockdown       202 countries,    Incidence         22 Jan-10 May    β coefficient −235.8 (standard error −11.04),        Serious or
                            experiment                       22 018 people                       2020             P
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 Table 2 | Continued
                                               Public health                                        Study dura-                                                           Risk of
 Reference, country        Study design        measure        Sample size       Outcome             tion            Effect estimates: conclusions                         bias
 Guo et al,40 US           Natural             Business      50 states and one Rt                   29 Jan-31 July Relative risk 0.88 (95% confidence interval 0.86       Moderate
                           experiment          closure       territory (Virgin                      2020           to 0.89): associated with 12% decrease in risk
                                                             Islands)                                              of Rt*
 Voko et al,53 Europe      Natural             Physical      28 countries      Incidence            1 Feb-18 Apr Incidence rate ratio 1.23 (95% confidence                Moderate
                           experiment          distancing                                           2020           interval 1.19 to 1.28), 0.98 (0.97 to 0.99): 26%
                                                                                                                   decrease in incidence*
 Van den Berg et           Retrospective       Physical           99 390 staff      Incidence       24 Sep 2020- ≥3 v ≥6 feet adjusted incidence rate ratio 1.01          Moderate
 al,37 US                  cohort              distancing                           (adjusted)      27 Jan 2021 (95% confidence interval 0.75 to 1.36), larger
                                                                                                                   physical distancing not associated with lower
                                                                                                                   rates of SARS-CoV-2*‡
 Xu et al,60 China         Cross sectional     Physical           8158 people       Incidence       22 Feb-5 Mar Relative risk 2.63 (95% confidence interval 1.48         Moderate
                           comparative         distancing                                           2020           to 4.67): significantly increased risk of infection*
 Doung-Ngern et al,63      Case-control        Physical           211 cases, 839    Incidence       1-31 Mar       >1m physical distance adjusted odds ratio              Serious or
 Thailand                                      distancing         controls                          2020           0.15; 95% confidence interval 0.04 to 0.63)):          critical
                                                                                                                   associated with lower risk of SARS-CoV-2
                                                                                                                   infection*
 Wang et al,57 China       Retrospective       Physical           335 people        Incidence       28 Feb-27 Mar Odds ratio 18.26 (95% confidence interval 3.93          Moderate
                           cohort              distancing                           (proportions    2020           to 84.79): risk of household transmission was
                                                                                    assessed as                    18 times higher with frequent daily close contact
                                                                                    attack rate†)                  with the primary case*
 Alimohamadi et al,47      Quasi-              Physical           NS                Incidence,      20 Feb-13      Incidence β coefficient −1.70 (95% confidence          Serious or
 Iran                      experimental        distancing                           mortality       May 2020       interval −2.3 to 1.1), mortality β coefficient         critical
                                                                                                                   −0.07 (−0.05 to −0.10): reduced incidence and
                                                                                                                   mortality*
 Quaife et al,61 Africa    Cross-sectional     Physical           237 cases         R0              1 -31 May      R0: pre-intervention 2.64, post-intervention 0.60      Moderate
                           comparative         distancing                                           2020           (interquartile range 0.50-0.68): 2.04 decrease
                                                                                                                   in R0
 Guo et al,40 US           Natural             Physical           50 states and one Rt              29 Jan-31 Jul Relative risk 0.88 (95% confidence interval 0.86        Moderate
                           experiment          distancing         territory (Virgin                 2020           to 0.89): associated with a 12% decrease in risk
                                                                  Islands)                                         of Rt*
R0=reproductive number; Rt=time varying reproductive number.
*Interpretation of findings as reported in the original manuscript.
†Percentage of individuals who tested positive over a specified period.
‡Not an effective intervention.

                                       retrospective cohort study observed a 14.1% reduction                 reported that lockdown was associated with an 11%
                                       in risk after implementation of universal lockdown                    reduction in transmission of SARS-CoV-2 (relative risk
                                       (table 2).46 These studies were rated at high risk of                 0.89, 95% confidence interval 0.88 to 0.91).40 All the
                                       bias52 and moderate risk of bias46 56 (fig 2).                        studies were rated at low risk of bias33 39 to moderate
                                                                                                             risk40 64 (fig 2).
                                       Lockdown and covid-19 mortality
                                       The three studies that assessed universal lockdown                    Travel related measures
                                       and covid-19 mortality generally reported a decrease                  Restricted travel and border closures
                                       in mortality (table 2).35 38 42 A natural experiment study            Border closure was assessed in one natural experiment
                                       involving 45 US states reported a decrease in covid-19                study involving nine African countries (table 3).62
                                       related mortality of 2.0% (95% confidence interval                    Overall, the countries recorded an increase in the
                                       −3.0% to 0.9%) daily after lockdown had been made                     incidence of covid-19 after border closure. These
                                       mandatory.35 A Brazilian quasi-experimental study                     studies concluded that the implementation of border
                                       reported a 27.4% average difference in covid-19 related               closures within African countries had minimal effect
                                       mortality rates in the first 25 days of lockdown.42 In                on the incidence of covid-19. The study had important
                                       addition, a natural experiment study reported about                   limitations and was rated at serious or critical risk of
                                       30% and 60% reductions in covid-19 related mortality                  bias. In the US, a natural experiment study reported that
                                       post-lockdown in Italy and Spain over four weeks post-                restrictions on travel between states contributed about
                                       intervention, respectively.38 All three studies were                  11% to a reduction in SARS-CoV-2 transmission (table
                                       rated at moderate risk of bias (fig 2).                               3).36 The study was rated at moderate risk of bias (fig 2).

                                       Lockdown and transmission of SARS-CoV-2                               Entry and exit screening (virus or symptom screening)
                                       Four studies assessed universal lockdown and                          One retrospective cohort study assessed screening of
                                       transmission of SARS-CoV-2 during the first few                       symptoms, which involved testing 65 000 people for
                                       months of the pandemic (table 2). The decrease in                     fever (table 3).54 The study found that screening for
                                       reproductive number (R0) ranged from 1.27 in Italy                    fever lacked sensitivity (ranging from 18% to 24%)
                                       (pre-intervention 2.03, post-intervention 0.76)39 to                  in detecting people with SARS-CoV-2 infection. This
                                       2.09 in India (pre-intervention 3.36, post-intervention               translated to 86% of the population with SARS-CoV-2
                                       1.27),64 and 3.97 in China (pre-intervention 4.95, post-              remaining undetected when screening for fever. The
                                       intervention 0.98).33 A natural experiment from the US                study was rated at moderate risk of bias (fig 2).

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 Table 3 | Study characteristics and main results from studies that assessed individual travel measures
 Reference,                            Public health                         Outcome
 country           Study design        measure                 Sample size   measure    Study duration   Effect estimates: conclusions                        Risk of bias
 Emeto et al,62    Natural             Border closure          9 countries   Rt         14 Feb-19 Jul    See supplementary table for data on all countries:   Serious or
 Africa            experiment                                                           2020             minimal effect on reducing transmission (Rt)*†       critical
 Liu et al,58      Natural             Interstate travel   50 states     Rt             21 Jan-31 May    Risk ratio 0.89 (95% confidence interval 0.84 to     Moderate
 USA               experiment          restrictions                                     2020             0.95): contributed about 11% to reduction in Rt*
 Mitra et al,54    Retrospective       Screening for fever 65 000 people Daily growth   9 Mar-13 May     Sensitivity 24%: 86% of cases not detected—poor      Moderate
 Australia         cohort                                                rate           2020             sensitivity of identifying people with SARS-CoV-2*
R0=reproductive number; Rt=time varying reproductive number.
*Interpretation of findings as reported in the original manuscript.
†Not an effective intervention

                                        Multiple public health measures                                     small number of individual studies (
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                                Comparison with other studies                                   Empirical evidence from restricted travel and
                                Previous literature reviews have identified mask wearing     full border closures is also limited, as it is almost
                                as an effective measure for the containment of SARS-         impossible to study these strategies as single
                                CoV-2103; the caveat being that more high level evidence     measures. Current evidence from a recent narrative
                                is required to provide unequivocal support for the           literature review suggested that control of movement,
                                effectiveness of the universal use of face masks.104 105     along with mandated quarantine, travel restrictions,
                                Additional empirical evidence from a recent randomised       and restricting nationals from entering areas of
                                controlled trial (originally published as a preprint)        high infection, are effective measures, but only with
                                indicates that mask wearing achieved a 9.3% reduction        good compliance.122 A narrative literature review
                                in seroprevalence of symptomatic SARS-CoV-2 infection        of travel bans, partial lockdowns, and quarantine
                                and an 11.9% reduction in the prevalence of covid-19-        also suggested effectiveness of these measures,123
                                like symptoms.106 Another systematic review showed           and another rapid review further supported travel
                                stronger effectiveness with the use of N95, or similar,      restrictions and cross border restrictions to stop the
                                respirators than disposable surgical masks,107 and a         spread of SARS-CoV-2.124 It was impossible to make
                                study evaluating the protection offered by 18 different      such observations in the current review because of
                                types of fabric masks found substantial heterogeneity        limited evidence. A German review, however, suggested
                                in protection, with the most effective mask being            that entry, exit, and symptom screening measures to
                                multilayered and tight fitting.108 However, transmission     prevent transmission of SARS-CoV-2 are not effective
                                of SARS-CoV-2 largely arises in hospital settings in which   at detecting a meaningful proportion of cases,125 and
                                full personal protective measures are in place, which        another review using real world data from multiple
                                suggests that when viral load is at its highest, even the    countries found that border closures had minimal
                                best performing face masks might not provide adequate        impact on the control of covid-19.126
                                protection.51 Additionally, most studies that assessed          Although universal lockdowns have shown a
                                mask wearing were prone to important confounding             protective effect in lowering the incidence of covid-19,
                                bias, which might have altered the conclusions drawn         SARS-CoV-2 transmission, and covid-19 mortality,
                                from this review (ie, effect estimates might have been       these measures are also disruptive to the psychosocial
                                underestimated or overestimated or can be related to         and mental health of children and adolescents,127 global
                                other measures that were in place at the time the studies    economies,128 and societies.129 Partial lockdowns
                                were conducted). Thus, the extent of such limitations on     could be an alternative, as the associated effectiveness
                                the conclusions drawn remain unknown.                        can be high,125 especially when implemented early
                                   A 2020 rapid review concluded that quarantine is          in an outbreak,85 and such measures would be less
                                largely effective in reducing the incidence of covid-19      disruptive to the general population.
                                and covid-19 mortality. However, uncertainty over               It is important to also consider numerous sociopolitical
                                the magnitude of such an effect still remains,109            and socioeconomic factors that have been shown to
                                with enhanced management of quality quarantine               increase SARS-CoV-2 infection130 131 and covid-19
                                facilities for improved effective control of the             mortality.132 Immigration status,82 economic status,81
                                                                                             101
                                epidemics urgently needed.110 In addition, findings              and poverty and rurality98 can influence individual
                                on the application of school and workplace closures          and community compliance with public health
                                are still inconclusive. Policy makers should be              measures. Poverty can impact the ability of communities
                                aware of the ambiguous evidence when considering             to physically distance,133 especially in crowded living
                                school closures, as other potentially less disruptive        environments,134 135 as well as reduce access to personal
                                physical distancing interventions might be more              protective measures.134 135 A recent study highlights
                                appropriate.21 Numerous findings from studies on             that “a one size fits all” approach to public health
                                the efficacy of school closures showed that the risk         measures might not be effective at reducing the spread
                                of transmission within the educational environment           of SARS-CoV-2 in vulnerable communities136 and could
                                often strongly depends on the incidence of covid-19          exacerbate social and economic inequalities.135 137
                                in the community, and that school closures are most          As such, a more nuanced and community specific
                                successfully associated with control of SARS-CoV-2           approach might be required. Even though screening is
                                transmission when other mitigation strategies are in         highly recommended by WHO138 because a proportion
                                place in the community.111-117 School closures have          of patients with covid-19 can be asymptomatic,138
                                been reported to be disruptive to students globally and      screening for symptoms might miss a larger proportion
                                are likely to impair children’s social, psychological,       of the population with covid-19. Hence, temperature
                                and educational development118 119 and to result in          screening technologies might need to be reconsidered
                                loss of income and productivity in adults who cannot         and evaluated for cost effectiveness, given such measures
                                work because of childcare responsibilities.120               are largely depended on symptomatic fever cases.
                                   Speculation remains as how best to implement
                                physical distancing measures.121 Studies that assess         Strengths and limitations of this review
                                physical distancing measures might interchangeably           The main strength of this systematic review was the
                                study physical distancing with lockdown35 52 56 64           use of a comprehensive search strategy to identify and
                                and other measures and thus direct associations are          select studies for review and thereby minimise selection
                                difficult to assess.                                         bias. A clinical epidemiologist developed the search

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           strategy, which was validated by two senior medical          covid-19. The narrative results of this review indicate
           librarians. This review followed a comprehensive             an effectiveness of both individual or packages of
           appraisal process that is recommended by the                 public health measures on the transmission of SARS-
           Cochrane Collaboration31 to assess the effectiveness         CoV-2 and incidence of covid-19. Some of the public
           of public health measures, with specifically validated       health measures seem to be more stringent than
           tools used to independently and individually assess          others and have a greater impact on economies and
           the risk of bias in each study by study design.              the health of populations. When implementing public
              This review has some limitations. Firstly, high quality   health measures, it is important to consider specific
           evidence on SARS CoV-2 and the effectiveness of public       health and sociocultural needs of the communities
           health measures is still limited, with most studies          and to weigh the potential negative effects of the
           having different underlying target variables. Secondly,      public health measures against the positive effects
           information provided in this review is based on current      for general populations. Further research is needed to
           evidence, so will be modified as additional data             assess the effectiveness of public health measures after
           become available, especially from more prospective           adequate vaccination coverage has been achieved. It
           and randomised studies. Also, we excluded studies            is likely that further control of the covid-19 pandemic
           that did not provide certainty over the effect measure,      depends not only on high vaccination coverage and
           which might have introduced selection bias and limited       its effectiveness but also on ongoing adherence to
           the interpretation of effectiveness. Thirdly, numerous       effective and sustainable public health measures.
           studies measured interventions only once and others          We thank medical subject librarians Lorena Romero (LR) and Marshall
           multiple times over short time frames (days v month, or      Dozier (MD) for their expert advice and assistance with the study
           no timeframe). Additionally, the meta-analytical portion     search strategy.
           of this study was limited by significant heterogeneity       Contributors: ST, DG, DI, DL, and ZA conceived and designed the
                                                                        study. ST, DG, SS, AM, HW, WX, JR, ET, AM, XL, XZ, and IME collected
           observed across studies, which could neither be
                                                                        and screened the data. ST, DG, and DI acquired, analysed, or
           explored nor explained by subgroup analyses or meta-         interpreted the data. ST, HW, and SS drafted the manuscript. All
           regression. Finally, we quantitatively assessed only         authors critically revised the manuscript for important intellectual
                                                                        content.. XL and ST did the statistical analysis. NA obtained funding.
           publications that reported individual measures; studies
                                                                        LR and MD provided administrative, technical, or material support. ST
           that assessed multiple measures simultaneously were          and DI supervised the study. ST and DI had full access to all the data in
           narratively analysed with a broader level of effectiveness   the study and take responsibility for the integrity of the data and the
                                                                        accuracy of the data analysis. ST is the guarantor. The corresponding
           (see supplementary material 3, table 3). Also, we
                                                                        author attests that all listed authors meet authorship criteria and that
           excluded studies in languages other than English.            no others meeting the criteria have been omitted.
                                                                        Funding: No funding was available for this research. ET is supported
           Methodological limitations of studies included in            by a Cancer Research UK Career Development Fellowship (grant No
           the review                                                   C31250/A22804). XZ is supported by The Darwin Trust of Edinburgh.

           Several studies failed to define and assess for              Competing interests: All authors have completed the ICMJE uniform
                                                                        disclosure form at www.icmje.org/disclosure-of-interest/and declare: ET
           potential confounders, which made it difficult               is supported by a Cancer Research UK Career Development Fellowship
           for our review to draw a one directional or causal           and XZ is supported by The Darwin Trust of Edinburgh; no financial
           conclusion. This problem was mainly because we               relationships with any organisations that might have an interest in the
                                                                        submitted work in the previous three years; and no other relationships
           were unable to study only one intervention, given that       or activities that could appear to have influenced the submitted work.
           many countries implemented several public health             Ethical approval: Not required.
           measures simultaneously; thus it is a challenge to           Data sharing: No additional data available.
           disentangle the impact of individual interventions (ie,      The lead author (ST) affirms that the manuscript is an honest,
           physical distancing when other interventions could           accurate, and transparent account of the study reported; no important
           be contributing to the effect). Additionally, studies        aspects of the study have been omitted. Dissemination to participants
                                                                        and related patient and public communities: It is anticipated to
           measured different primary outcomes and in varied            disseminate the results of this research to wider community via press
           ways, which limited the ability to statistically analyse     release and social media platforms.
           other measures and compare effectiveness.                    Provenance and peer review: Not commissioned; externally peer
              Further pragmatic randomised controlled trials and        reviewed.
           natural experiment studies are needed to better inform       This is an Open Access article distributed in accordance with the
                                                                        Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
           the evidence and guide the future implementation of          which permits others to distribute, remix, adapt, build upon this work
           public health measures. Given that most measures             non-commercially, and license their derivative works on different
           depend on a population’s adherence and compliance,           terms, provided the original work is properly cited and the use is non-
                                                                        commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
           it is important to understand and consider how
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the bmj | BMJ 2021;375:e068302 | doi: 10.1136/bmj-2021-068302                                                                                                                          13
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